Characterising the TP53-deleted subgroup of chronic lymphocytic leukemia: an analysis of additional cytogenetic abnormalities detected by interphase fluorescence in situ hybridisation and array-based comparative genomic hybridisation.
Deletion of the TP53 gene on chromosome 17p13.1 is the prognostic factor associated with the shortest survival in CLL. We used array-based comparative genomic hybridisation (arrayCGH) to identify additional DNA copy number changes in peripheral blood samples from 74 LRF CLL4 trial patients, 37 with >or=5% and 37 without TP53-deleted cells. ArrayCGH reliably detected deletions on 17p, including the TP53 locus, in cases with >or=50%TP53-deleted cells detected by fluorescence in situ hybridisation, plus seven additional cases with deleted regions on 17p excluding TP53. Losses on chromosomal regions 18p and/or 20p were found exclusively in cases with >or=5%TP53-deleted cells (p<0.001), 38% having one or both losses. The incidence of additional cytogenetic abnormalities, reflecting an increased chromosomal instability, was higher in >or=5%TP53-deleted cases (p=0.02). In particular, amplification of 2p and deletion of 6q were both more frequent. Cases with >20%TP53-deleted cells had the worst prognosis in the LRF CLL4 trial.
Rudenko
Hannah C
HC
Section of Haemato-Oncology, The Institute of Cancer Research (ICR), Sutton, Surrey, London, UK.
Else
Monica
M
Dearden
Claire
C
Brito-Babapulle
Vasantha
V
Jones
Chris
C
Dexter
Tim
T
Fenwick
Kerry
K
Mackay
Alan
A
Ashworth
Alan
A
Matutes
Estella
E
Gonzalez
David
D
Catovsky
Daniel
D
Morgan
Gareth J
GJ
D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002890:Chromosomes, Human, Pair 20; D002986:Clinical Trials as Topic; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53